1. Field of the Invention
This invention relates to a method for at least reducing the amount of furanocoumarins in grapefruit juice using edible fungal hyphae and to products produced by the method for at least reducing the amount of furanocoumarins in grapefruit juice.
2. Description of the Related Art
Furanocoumarins are a class of phenolic compounds produced by the Apiaceae and Rutacea families and have been extensively studied for their biological activities and clinical applications. The furanocoumarins are known to play roles in intestinal P450 enzyme inhibition, DNA photocrosslinking, and defense mechanisms as natural toxic compounds (Afek et al., Phytochemistry 50:1129-1132, 1999; Guo et al., Drug Metab. Dispos. 28:766-771, 2000; Oliva et al., J. Agric. Food Chem. 51:890-896, 2003; Santana et al., Curr. Med. Chem. 11:3239-3261, 2004; Weimin et al., Proc. Natl. Acad. Sci. USA 100:14593-14598, 2003). Grapefruit juice contains three major furanocoumarins, including bergamottin, 6′,7′-dihydroxybergamottin, and 6′,7′-epoxybergamottin, as well as numerous minor-occurring furanocoumarins including dimmers and hetero-dimers of bergamottin, 6′,7′-epoxybergamottin, and 6′,7′-dihydroxybergamottin (Manthey et al., J. Agric. Food Chem. 53:5158-5163, 2005; Manthey et al., Proc. Fla. State Hortic. Soc. 119:361-366, 2006). These furanocoumarins are known to be involved in the “grapefruit-drug interactions”, in which they act as inhibitors of intestinal P450 CYP3A, the enzyme responsible for the metabolism of many widely-prescribed medications. In certain cases, this inhibition would cause a significant reduction in the first pass metabolism of certain drugs and this strongly modulates oral bioavailability. (Guo et al., Drug Metab. Dispos. 28:766-771, 2000; Wangensteen et al., Eur. J. Clin. Pharmacol. 58:663-668, 2003; Maskalyk, Can. Med. Assoc. J. 168:279-280, 2002). First pass metabolism refers to the metabolism of drugs before it is available for uptake into the body, while oral bioavailability is the amount of drug delivered to the subject's blood stream. The grapefruit-drug interaction basically causes too much of the drug being absorbed to the body. Despite the fact that grapefruit juice inhibits only enteric CYP3A4, a number of drugs with potential clinical importance are known to interact with grapefruit juice. For some drugs such as clyclosporine, simvastatin, and lovastatin, warnings or precautionary statements regarding the potential for a grapefruit juice interaction has been included in the product labeling. Cyclosporine and other drugs with a narrow therapeutic index are of particular concern because the extent of an interaction with grapefruit juice is unpredictable. This is due in part to interindividual variation in baseline enteric CYP3A4 content or activity and to variable concentrations of the active inhibitors in the different brands and preparations of grapefruit juice.
Microorganisms have been widely applied to the detoxification or elimination of certain classes of compounds via metabolism or biosorption (Bejaoui et al., J. Appl. Microbiol. 97:1038-1044, 2004; Bejaoui et al., J. Agric. Food Chem. 53:8224-8229, 2005; Denizli et al., Bioresour. Technol. 96:59-62, 2005; El-Nezami et al., Appl. Environ. Microbiol. 68:3545-3549, 2002; Farooq and Tahara, Curr. Top. Phytochem. 2:1-33, 1999). For example, adsorption of ochratoxin A, zearalenone, α-zearalenol, and chlorophenols from solutions by autoclaved fungi has been reported. Thus, similar removal of furanocoumarins from grapefruit juice by fungi may also be a practical method to reduce the grapefruit-drug interactions in humans.
These interactions have adversely affected the grapefruit industry, and have led to a need to develop a process to remove furanocoumarins from grapefruit juice in a manner that retains much of the original juice sensory attributes. Currently, there is no satisfactory means of producing a furanocoumarin-free citrus juice. Recently, in order to reduce the risk of citrus juice-drug interaction, there have been attempts to eliminate furanocoumarins from juice using chemical and physical methods (Paine et al., Am. J. Clin. Nutr. 83:1097-1105, 2006; Uesawa and Mohri, Biol. Pharm. Bull. 29:1286-1289, 2006a, Uesawa and Mohri, Biol. Pharm. Bull. 29:2274-2278, 2006b). The chemical method, developed by Paine et al. (2006), would be complicated and expensive, while UV and heat treatments, used by Uesawa and Mohri (2006a and 2006b), may produce unknown artifacts.
Although there have been attempts to remove furanocoumarins from grapefruit juice, there still remains a need in the art for a more effective removal method for citrus juice furanocoumarins. Therefore, the present invention, different from prior art systems, provides a method for quantitative, inexpensive removal of the furanocoumarins with only minimal effects to the juice quality and taste.